Uncontrolled cell division is an indispensable event in tumor progression, and numerous molecules involved in this process have been the focus of intense investigation in tumor biology. Cyclins, molecules that orchestrate normal cell cycle progression, are abnormally overexpressed in various human cancers. We review evidence that the immune system recognizes some abnormally expressed cyclins as...

E type cyclins (E1 and E2) are believed to drive cell entry into the S phase. It is widely assumed that the two E type cyclins are critically required for proliferation of all cell types. Here, we demonstrate that E type cyclins are largely dispensable for mouse development. However, endoreplication of trophoblast giant cells and megakaryocytes is severely impaired in the absence of cyclin E. C...

D-type cyclins are induced in response to mitogens and are essential and rate-limiting for G1 phase progression in normal mammalian cells. Macrophages proliferating in response to colony-stimulating factor-1 (CSF-1) express cyclin D1 and to a lesser extent cyclin D2 but not cyclin D3. Previously we showed that the macrophage-activating agent lipopolysaccharide (LPS) blocks CSF-1-induced prolife...

The D-type cyclins and their major kinase partners CDK4 and CDK6 regulate G0-G1-S progression by contributing to the phosphorylation and inactivation of the retinoblastoma gene product, pRB. Assembly of active cyclin D-CDK complexes in response to mitogenic signals is negatively regulated by INK4 family members. Here we show that although all four INK4 proteins associate with CDK4 and CDK6 in v...

PURPOSE Nerve growth factor (NGF) plays an important role in promoting the healing of corneal wounds. However, the molecular mechanism by which NGF functions is unknown. We investigated the possible effects of NGF on phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) and mitogen activated protein kinase (MAPK)/extracellular signal-regulated kinase (Erk) pathways and cell growth in huma...

Progression through meiosis requires two waves of maturation promoting factor (MPF) activity corresponding to meiosis I and meiosis II. Frog oocytes contain a pool of inactive "pre-MPF" consisting of cyclin-dependent kinase 1 bound to B-type cyclins, of which we now find three previously unsuspected members, cyclins B3, B4 and B5. Protein synthesis is required to activate pre-MPF, and we show h...

β-Cell regeneration is a key goal of diabetes research. Progression through the cell cycle is associated with retinoblastoma protein (pRb) inactivation via sequential phosphorylation by the "early" cyclins and cyclin-dependent kinases (cdks) (d-cyclins cdk4/6) and the "late" cyclins and cdks (cyclin A/E and cdk1/2). In β-cells, activation of either early or late G1/S cyclins and/or cdks is an e...

Cyclins play important roles in cell division and cell expansion. They also interact with cyclin-dependent kinases to control cell cycle progression in plants. Our genome-wide analysis identified 52 expressed cyclin genes in tomato. Phylogenetic analysis of the deduced amino sequences of tomato and Arabidopsis cyclin genes divided them into 10 types, A-, B-, C-, D-, H-, L-, T-, U-, SDS- and J18...

The response of cells to extracellular mitogenic signals and commitment to enter G1 phase, are regulated by the D-type cyclins (D1, D2 and D3). Once induced they heterodimerize with and activate either cyclin dependent kinase 4 or 6 (CDK4 or CDK6). Cyclin D-CDK4 and D-CDK6 kinases phosphorylate and inactivate the retinoblastoma family of proteins, leading to release and derepression of E2F tran...